ATF7IP/SETDB1-mediated epigenetic programming regulates thymic homing and T lymphopoiesis of hematopoietic progenitors during embryogenesis.

ABSTRACT: T lymphocytes, which are essential for cell-mediated immunity in vertebrates, rely on thymic seeding of lymphoid progenitors for commitment, differentiation and maturation. However, the epigenetic programming of lymphoid-primed progenitor migration and differentiation is incompletely understood. Here, we show that zebrafish embryos lacking the epigenetic modulator Atf7ip or Setdb1 methyltransferase exhibit decreased thymic homing and differentiation of lymphoid progenitor cells. We show that Atf7ip regulates T cell progenitor homing and differentiation via Setdb1-triggered H3K9 trimethylation. Atf7ip interacts with Setdb1 to catalyze H3K9me3 modification of the key immune regulator bach2b to derepress the expression of ccr9a and irf4a, thereby promoting lymphoid progenitor homing and intra

SUBMITTER: Chen W 

PROVIDER: S-EPMC12267628 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature